DESCRIPTION (Verbatim from applicant's abstract): Synapses represent polarized,[unreadable] specialized intercellular junctions and constitute the major points of[unreadable] communication between neurons in the brain. At a synapse, the presynaptic[unreadable] neuron secretes neurotransmitters that are then recognized by the postsynaptic[unreadable] cell. Synaptic junctions are formed by interactions between pre- and[unreadable] postsynaptic membranes but little is known about the molecular basis for these[unreadable] interactions. Alpha- and beta-neurexins constitute a polymorphic family of[unreadable] neuron-specific, cell surface proteins that are expressed from three genes.[unreadable] Indirect evidence suggests that these proteins function as cell adhesion and[unreadable] signaling molecules in synaptic junctions. The evidence includes the[unreadable] observation of a large number of neurexin isoforms generated by alternative[unreadable] splicing (>1000 isoforms), the finding that an alternatively-spliced subset of[unreadable] beta-neurexins binds to a novel neuronal cell adhesion molecule called[unreadable] neuroligin, which is also localized to synapses, and the fact that[unreadable] intracellular complexes of synaptic proteins assemble on neurexins via[unreadable] PDZ-domain interactions. Furthermore, knockout mice revealed that the deletion[unreadable] of alpha-neurexins causes a selective deficit in symmetric synapses. The[unreadable] overall hypothesis that will be tested in the current grant application is that[unreadable] neurexins function as synaptic cell adhesion and recognition molecules and[unreadable] contribute to the formation and maintenance of synaptic junctions. Four[unreadable] specific aims are proposed to test this hypothesis. The first specific aim will[unreadable] examine the precise localization of neurexins. The second analyzes their[unreadable] functions genetically in knockout mice. The third specific aim will[unreadable] characterize the functions of neurexins as cell adhesion molecules and[unreadable] signaling receptors, and the fourth specific aim will study the intracellular[unreadable] interactions of neurexins with PDZ-domain proteins that link the neurexins to[unreadable] synaptic vesicle traffic and the actin cytoskeleton. Together, these[unreadable] experiments will provide insight into the function of this highly conserved[unreadable] neuron-specific family of proteins and extend our understanding of how synapses[unreadable] are formed and maintained.[unreadable]